Neurogenic vasodilatation and plasma leakage in the skin.
1. Primary afferent nerve fibers control cutaneous blood flow and vascular permeability by releasing vasoactive peptides. These vascular reactions and the additional recruitment of leukocytes are commonly embodied in the term neurogenic inflammation. 2. Calcitonin gene-related peptide (CGRP) acting via CGRP1 receptors is the principal transmitter of neurogenic dilatation of arterioles whereas substance P (SP) and neurokinin A (NKA) acting via NK1 receptors mediate the increase in venular permeability. 3. Neurogenic vasodilatation and plasma protein leakage play a role in inflammation because many inflammatory and immune mediators including interleukin-1 beta, nitric oxide, prostanoids, protons, bradykinin, histamine, and 5-hydroxytryptamine can stimulate peptidergic afferent nerve fibers or enhance their excitability. 4. Neurogenic inflammatory reactions can be suppressed by alpha 2-adrenoceptor agonists, histamine acting via H1 receptors, 5-hydroxytryptamine acting via 5-HT1B receptors, opioid peptides, and somatostatin through prejunctional inhibition of peptide release from vasoactive afferent nerve fibers. CGRP, SP, and NKA receptor antagonists are powerful pharmacological tools to inhibit neurogenic inflammation at the postjunctional level. 5. Imbalance between the facilitatory and inhibitory influences on afferent nerve activity has a bearing on chronic inflammatory disease. Impaired nerve function represents a deficit in skin homeostasis while neuronal overactivity is a factor in allergic and hyperreactive disorders of the skin.
Holzer
P
P
University of Graz, Department of Experimental and Clinical Pharmacology, Austria. peter.holzer@kfunigraz.ac.at
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000502:physiology; D002199:Capillary Permeability / Q000502:physiology*; D006801:Humans; D015288:Neurokinin A / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D013373:Substance P / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D009479:Neuropeptides; D013373:Substance P; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide